Human Reproduction Vol.20, No.10 pp.

26982704, 2005

doi:10.1093/humrep/dei135

Advance Access publication June 24, 2005.

ESHRE guideline for the diagnosis and treatment

of endometriosis
Stephen Kennedy1,10, Agneta Bergqvist2, Charles Chapron3, Thomas DHooghe4,
Gerard Dunselman5, Robert Greb6, Lone Hummelshoj7, Andrew Prentice8
and Ertan Saridogan9 on behalf of the ESHRE Special Interest Group for Endometriosis
and Endometrium Guideline Development Group*
1

University of Oxford, Oxford, UK, 2Karolinska Institutet, Stockholm, Sweden, 3Clinique Universitaire Baudelocque, Paris, France,
Leuven University, Leuven, Belgium, 5Maastricht University, Maastricht, The Netherlands, 6Muenster University Hospital, Muenster,
Germany, 7Endometriose Foreningen, Denmark, 8University of Cambridge, Cambridge, UK and 9University College Hospital, London, UK
4

10

To whom correspondence should be addressed at: Nuffield Department of Obstetrics and Gynaecology, University of Oxford,
John Radcliffe Hospital, Oxford OX3 9DU, UK. E-mail: Stephen.kennedy@obs-gyn.ox.ac.uk

Key words: diagnosis/endometriosis/ESHRE guidelines/treatment

*The manuscript was prepared by the first author; all other authors contributed equally and are listed in alphabetical order. Guideline Development
Group: Agneta Bergqvist, Karolinska Institutet, Stockholm (Chair), Charles
Chapron, Clinique Universitaire Baudelocque, Paris (Working party), Gerard
Dunselman, Maastricht University (Working party), Robert Greb, Muenster
University Hospital (Working party), Thomas DHooghe, Leuven University
(Vice-Chair), Lone Hummelshoj, Endometriose Foreningen, Denmark (Working

2698

party), Stephen Kennedy, University of Oxford (Report writer), Philippe

Koninckx, Leuven University and University of Oxford (Contributor), Roberto
Matorras, Pas Vasco University (Contributor), Michael Mueller, University of
Berne (Contributor), Andrew Prentice, University of Cambridge (Working
party), Ertan Saridogan, University College Hospital, London (Working
party), Juan Garcia-Velasco, Instituto Valenciano de Infertilidad, Madrid
(Contributor).

Published by Oxford University Press 2005 on behalf of the European Society of Human Reproduction and Embryology.

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The objective was to develop recommendations for the diagnosis and treatment of endometriosis and its associated
symptoms. A working group was convened comprised of practising gynaecologists and experts in evidence-based
medicine from Europe, as well as an endometriosis self-help group representative. After reviewing existing evidencebased guidelines and systematic reviews, the expert panel met on three occasions for a day during which the guideline
was developed and refined. Recommendations based solely on the clinical experience of the panel were avoided as
much as possible. The entire ESHRE Special Interest Group for Endometriosis and Endometrium was given the
opportunity to comment on the draft guideline, after which it was available for comment on the ESHRE website for
3 months. The working group then ratified the guideline by unanimous or near-unanimous voting; finally, it was
approved by the ESHRE Executive Committee. The guideline will be updated regularly, and will be made available
at http://www.endometriosis.org/guidelines.html with hyperlinks to the supporting evidence, and the relevant references and abstracts. For women presenting with symptoms suggestive of endometriosis, a definitive diagnosis of most
forms of endometriosis requires visual inspection of the pelvis at laparoscopy as the gold standard investigation.
However, pain symptoms suggestive of the disease can be treated without a definitive diagnosis using a therapeutic
trial of a hormonal drug to reduce menstrual flow. In women with laparoscopically confirmed disease, suppression of
ovarian function for 6 months reduces endometriosis-associated pain; all hormonal drugs studied are equally effective
although their side-effects and cost profiles differ. Ablation of endometriotic lesions reduces endometriosis-associated
pain and the smallest effect is seen in patients with minimal disease; there is no evidence that also performing laparoscopic uterine nerve ablation (LUNA) is necessary. In minimalmild endometriosis, suppression of ovarian function
to improve fertility is not effective, but ablation of endometriotic lesions plus adhesiolysis is effective compared to
diagnostic laparoscopy alone. There is insufficient evidence available to determine whether surgical excision of moderatesevere endometriosis enhances pregnancy rates. IVF is appropriate treatment especially if there are coexisting
causes of infertility and/or other treatments have failed, but IVF pregnancy rates are lower in women with endometriosis than in those with tubal infertility. The management of severe/deeply infiltrating endometriosis is complex and
referral to a centre with the necessary expertise is strongly recommended. Patient self-help groups can provide invaluable counselling, support and advice.

Guideline for diagnosis and treatment of endometriosis

Introduction

Recommendations

Endometriosis is defined as the presence of endometrial-like

tissue outside the uterus, which induces a chronic, inflammatory reaction. The condition is predominantly found in
women of reproductive age, from all ethnic and social
groups. The associated symptoms can impact on general
physical, mental and social well-being. Therefore, it is vital
to take careful note of the womans complaints, and to give
her time to express her concerns and anxieties as in other
chronic diseases. Some women, however, have no symptoms at all.
Treatment must be individualized, taking the clinical
problem in its entirety into account, including the impact of
the disease and the effect of its treatment on quality of life.
Pain symptoms may persist despite seemingly adequate
medical and/or surgical treatment of the disease. In such
circumstances, a multi-disciplinary approach involving a
pain clinic and counselling should be considered early in the
treatment plan. It is also important to involve the woman in
all decisions; to be flexible in diagnostic and therapeutic
thinking; to maintain a good relationship with the woman,
and to seek advice where appropriate from more experienced
colleagues or refer the woman to a centre with the necessary
expertise to offer all available treatments in a multi-disciplinary
context, including advanced laparoscopic surgery and
laparotomy.

The highest level of available evidence was used to form all the
recommendations contained in this guideline. The evidence
was graded using standard criteria shown in Table I.
This scale, which was developed to apply to studies about
the effectiveness of health-care interventions, is only a guide to
the validity and relevance of evidence. Other questions may be
more appropriately addressed by different study designs: for
example, a question about the predictive power of an investigation is best answered with observational data.
Recommendations were based on, and linked to, the supporting
evidence, or, where necessary, the informal consensus of the working group. The strength of evidence corresponding to each level
of recommendation is shown in Table II. Regarding diagnostic
tests specifically, a recommendation based on the existence of a
well-conducted systematic review was assessed as grade A.

The guideline was commissioned by the ESHRE Special Interest

Group (SIG) on Endometriosis and Endometrium, and
developed by a working group. No systematic attempt was
made to search the published literature independently of the
following sources:

Clinical Evidence: the monthly, updated directory of

evidence on the effects of clinical interventions, published by
the BMJ Publishing Group (UK).
http://www.clinicalevidence.com.
NICE Guideline on the assessment and treatment for
people with fertility problems, produced by the National Institute
for Clinical Evidence.
http://www.nice.org.uk/Docref.asp?d=106333.
Green Top Guideline on the investigation and management
of endometriosis, produced by the Royal College of Obstetricians and Gynaecologists.
http://www.rcog.org.uk/guidelines.asp?PageID =106& GuidelineID.
Guideline on the diagnosis and treatment of endometriosis, produced by the Dutch Society of Obstetrics and
Gynaecology.
http://www.nvog.nl/files/endometriose041026.pdf.
Consensus statement for the management of chronic
pelvic pain and endometriosis, produced by a group of US
gynaecologists.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=
Retrieve& db=PubMed&list_uids=12413979&dopt=Abstract.

The most commonly affected sites are the pelvic organs and peritoneum, although other parts of the body such as the lungs are
occasionally affected. The extent of the disease varies from a few,
small lesions on otherwise normal pelvic organs to large, ovarian
endometriotic cysts (endometriomas) and/or extensive fibrosis
and adhesion formation causing marked distortion of pelvic anatomy. Disease severity is assessed by simply describing the findings at surgery or quantitatively, using a classification system
such as the one developed by the American Society for Reproductive Medicine (ASRM) (1997). There is no correlation
between such systems and the type or severity of pain symptoms.
Table I. Hierarchy of evidence
Level

Evidence

1a

Systematic review and meta-analysis of randomized

controlled trials (RCT)
At least one RCT
At least one well-designed controlled study without
randomization
At least one other type of well-designed
quasi-experimental study
Well-designed, non-experimental, descriptive studies,
such as comparative studies, correlation studies or case
studies
Expert committee reports or opinions and/or clinical
experience of respected authorities

1b
2a
2b
3
4

Table II. Strength of evidence corresponding to each level of

recommendation
Grade

Strength of evidence

A
B

Directly based on level 1 evidence

Directly based on level 2 evidence or extrapolated
recommendation from level 1 evidence
Directly based on level 3 evidence or extrapolated
recommendation from either level 1 or level 2 evidence
Directly based on level 4 evidence or extrapolated
recommendation from either level 1, 2 or 3 evidence
Good practice point based upon the views of the Guideline
Development Group

C
D
GPP

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Sources

Localization and appearance of endometriosis

S.Kennedy et al.

Endometriosis typically appears as superficial powderburn or gunshot lesions on the ovaries, serosal surfaces and
peritoneum black, dark-brown, or bluish puckered lesions,
nodules or small cysts containing old haemorrhage surrounded
by a variable extent of fibrosis. Atypical or subtle lesions are
also common, including red implants (petechial, vesicular,
polypoid, haemorrhagic, red flame-like) and serous or clear
vesicles. Other appearances include white plaques or scarring
and yellow-brown peritoneal discoloration of the peritoneum.
Endometriomas usually contain thick fluid like tar; such
cysts are often densely adherent to the peritoneum of the ovarian fossa and the surrounding fibrosis may involve the tubes and
bowel. Deeply infiltrating endometriotic nodules extend >5 mm
beneath the peritoneum and may involve the uterosacral ligaments, vagina, bowel, bladder or ureters. The depth of infiltration is related to the type and severity of symptoms (Koninckx
et al., 1991; Porpora et al., 1999; Chapron et al., 2003a).

Histology
Positive histology confirms the diagnosis of endometriosis;
negative histology does not exclude it. Whether histology should
be obtained if peritoneal disease alone is present is controversial:
visual inspection is usually adequate but histological confirmation
of at least one lesion is ideal. In cases of ovarian endometrioma
(>3 cm in diameter), and in deeply infiltrating disease, histology
should be obtained to identify endometriosis and to exclude rare
instances of malignancy.

GPP

If the patient wants pain symptoms suggestive of endometriosis to

be treated without a definitive diagnosis, then a therapeutic trial of
a hormonal drug to reduce menstrual flow is appropriate (see
Empirical treatment section).

GPP

The management of severe/deeply infiltrating endometriosis is

complex. Therefore, if disease of such severity is suspected or
diagnosed, referral to a centre with the necessary expertise to offer
all available treatments in a multi-disciplinary context, including
advanced laparoscopic surgery and laparotomy, is strongly
recommended.

Symptoms
Establishing the diagnosis of endometriosis on the basis of
symptoms alone can be difficult because the presentation is so
variable and there is considerable overlap with other conditions
such as irritable bowel syndrome and pelvic inflammatory disease. As a result there is often a delay of several years between
symptom onset and a definitive diagnosis (Hadfield et al.,
1996; Arruda et al., 2003; Husby et al., 2003).
The following symptoms can be caused by endometriosis
based on clinical and patient experience: severe dysmenorrhoea; deep dyspareunia; chronic pelvic pain; ovulation pain;
cyclical or perimenstrual symptoms (e.g. bowel or bladder
associated) with or without abnormal bleeding; infertility; and
chronic fatigue. However, the predictive value of any one
symptom or set of symptoms remains uncertain as each of
these symptoms can have other causes, and a significant
proportion of affected women are asymptomatic.

Finding pelvic tenderness, a fixed retroverted uterus, tender

uterosacral ligaments or enlarged ovaries on examination is
suggestive of endometriosis. The diagnosis is more certain if
deeply infiltrating nodules are found on the uterosacral ligaments or in the pouch of Douglas, and/or visible lesions are
seen in the vagina or on the cervix. The findings may, however, be normal.
Deeply infiltrating nodules are most reliably
detected when clinical examination is
performed during menstruation (Koninckx
et al., 1996).

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For a definitive diagnosis of endometriosis,

visual inspection of the pelvis at laparoscopy
is the gold standard investigation, unless
disease is visible in the vagina or elsewhere.

Compared to laparoscopy, transvaginal

ultrasound (TVS) has no value in diagnosing
peritoneal endometriosis, but it is a useful tool
both to make and to exclude the diagnosis of
an ovarian endometrioma (Moore et al.,
2002). TVS may have a role in the diagnosis
of disease involving the bladder or rectum.

Systematic
review of
diagnostic
tests

Magnetic resonance imaging

Compared to laparoscopy, magnetic resonance
imaging (MRI) has limited value as a
diagnostic tool for endometriosis (Ang et al.,
submitted).

Systematic
review of
diagnostic
tests

Blood tests
A

Evidence
level 3

Serum CA-125 levels may be elevated in

endometriosis. However, compared to
laparoscopy, measuring serum CA-125 levels
has no value as a diagnostic tool (Mol et al.,
1998).

Systematic
review of
diagnostic
tests

Investigations to assess disease extent

Diagnosis
C

Ultrasound

Clinical signs

Investigations

GPP
Evidence
level 3

If there is clinical evidence of deeply infiltrating endometriosis,

ureteral, bladder and bowel involvement should be assessed.
Consideration should be given to performing MRI or ultrasound
(transrectal and/or transvaginal and/or renal), with or without
intravesical pressure (IVP) and barium enema studies depending
upon the individual circumstances, to map the extent of disease
present, which may be multi-focal.

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GPP

Guideline for diagnosis and treatment of endometriosis

when taken at mid-cycle. Other analgesics may be effective but

there is insufficient evidence to make recommendations.

Assessment of ovarian cysts

GPP

Local guidelines for the management of suspected

ovarian malignancy should be followed in cases of ovarian
endometrioma. Ultrasound scanning serum CA-125 testing
is usually used to try to identify rare instances of ovarian
cancer; however, CA-125 levels can be elevated in the presence
of endometriomas.

Hormonal treatment
A

Laparoscopy
Good surgical practice is to document in detail the type, location
and extent of all lesions and adhesions in the operative notes; ideal
practice is to record the findings on video or DVD.

GPP

There is insufficient evidence to justify timing the laparoscopy

at a specific time in the menstrual cycle, but it should not be
performed during or within 3 months of hormonal treatment so
as to avoid under-diagnosis.

The levonorgestrel intrauterine system (LNG-IUS) may be

effective at reducing endometriosis-associated pain (Vercellini
et al., 1999a), but there is insufficient evidence to make recommendations.
Duration of GnRH agonist treatment
A

All classification systems for endometriosis are

subjective and correlate poorly with pain
symptoms, but may be of value in infertility
prognosis and management (Chapron et al.,
2003b; DHooghe et al., 2003).

Evidence
level 3

At laparoscopy, deeply infiltrating endometriosis

may have the appearance of minimal disease,
resulting in an underestimation of disease
severity (Koninckx et al., 1994).

Evidence
level 3

Empirical treatment of pain symptoms without a definitive

diagnosis
Empirical treatment for pain symptoms presumed to be due to
endometriosis without a definitive diagnosis includes counselling,
adequate analgesia, nutritional therapy, progestagens or the
combined oral contraceptive (COC). It is unclear whether the
COC should be taken conventionally, continuously or in a tricycle
regimen. A GnRH agonist may be taken but this class of drug is
more expensive, and associated with more side-effects and
concerns about bone density.

Non-steroidal anti-inflammatory drugs

(NSAID) may be effective in reducing
endometriosis-associated pain (Kauppila et al.,
1979; Ylikorkala and Viinikka, 1983; Kauppila
and Ronnberg, 1985).

Evidence
level 1b

It is important to note that NSAIDs have significant sideeffects, including gastric ulceration and an anti-ovulatory effect

Evidence
level 1b

Depending upon the severity of disease found, ideal practice is to

diagnose and remove endometriosis surgically at the same time,
provided that pre-operative adequate consent has been obtained
(Redwine and Wright, 2001; Abbott et al., 2003; Chapron et al.,
2003b; Fedele et al., 2004).

There are no data to justify hormonal treatment prior to

surgery to improve the success of surgery (Muzii et al., 1996).
A

Treatment of endometriosis-associated pain

in confirmed disease
Non-steroidal anti-inflammatory drugs

Treatment for 3 months with a GnRH agonist

may be as effective as 6 months in terms of
pain relief (Hornstein et al., 1995). Treatment
for up to 2 years with combined estrogen
progestagen add-back appears to be effective
and safe in terms of pain relief and bone
density protection (Surrey and Hornstein, 2002).
However, careful consideration should be
given to the use of GnRH agonists in women
who may not have reached their maximum
bone density.

Surgical treatment
GPP

GPP

Evidence
level 1a

Ablation of endometriotic lesions plus

laparoscopic uterine nerve ablation (LUNA) in
minimalmoderate disease reduces
endometriosis-associated pain at 6 months
compared to diagnostic laparoscopy; the
smallest effect is seen in patients with minimal
disease (Jacobson et al., 2004a). However, there
is no evidence that LUNA is a necessary
component, as LUNA by itself has no effect on
dysmenorrhoea associated with endometriosis
(Vercellini et al., 2003a).

Evidence
level 1b

There are no data supporting the use of uterine suspension

but, in certain cases, there may be a role for pre-sacral neurectomy (Soysal et al., 2003).
GPP

Endometriosis-associated pain can be reduced by removing

the entire lesions in severe and deeply infiltrating disease.
If a hysterectomy is performed, bilateral salpingo-oophorectomy
should also be considered (Namnoum et al., 1995), provided
that all visible endometriotic tissue is removed at the same
time (Lefebvre et al., 2002).

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GPP

Suppression of ovarian function for 6 months

reduces endometriosis-associated pain. The
hormonal drugs investigatedCOC, danazol,
gestrinone, medroxyprogesterone acetate and
GnRH agonistsare equally effective but their
side-effects and cost profiles differ (Moore et al.,
2004; Prentice et al., 2004a,b; Selak et al., 2004).

S.Kennedy et al.

Post-operative treatment
A

Treatment with danazol or a GnRH agonist for

6 months after surgery reduces endometriosisassociated pain and delays recurrence at 12 and
24 months compared with placebo and
expectant management. However, postoperative treatment with a COC is not effective
(Telimaa et al., 1987; Parazzini et al., 1994;
Hornstein et al., 1997; Bianchi et al., 1999;
Morgante et al., 1999; Vercellini et al., 1999b;
Muzii et al., 2000; Busacca et al., 2001).

Evidence
level 3

Laparoscopic cystectomy for ovarian

endometriomas >4 cm diameter improves
fertility compared to drainage and coagulation
(Beretta et al., 1998; Chapron et al., 2002)
Coagulation or laser vaporization of
endometriomas without excision of the pseudocapsule is associated with a significantly
increased risk of cyst recurrence (Vercellini
et al., 2003b).

Evidence
level 1b

Evidence
level 4

Post-operative treatment
A

Treatment with danazol or a GnRH agonist after

surgery does not improve fertility compared
with expectant management (Parazzini et al.,
1994; Bianchi et al., 1999; Vercellini et al.,
1999b; Busacca et al., 2001).

Evidence
level 1b

Treatment of endometriosis-associated infertility in

confirmed disease
Treatment of endometriotic lesions
Assisted reproduction in endometriosis

Hormonal treatment

Intrauterine insemination
A

Suppression of ovarian function to improve

fertility in minimalmild endometriosis is not
effective and should not be offered for this
indication alone (Hughes et al., 2004). There is
no evidence of its effectiveness in more severe
disease.

Evidence
level 1a

Treatment with intrauterine insemination (IUI)

improves fertility in minimalmild
endometriosis: IUI with ovarian stimulation is
effective but the role of unstimulated IUI is
uncertain (Tummon et al., 1997).

Evidence
level 1b

IVF is appropriate treatment especially if tubal

function is compromised, if there is also male
factor infertility, and/or other treatments have
failed.

Evidence
level 2b

IVF pregnancy rates are lower in patients with

endometriosis than in those with tubal infertility
(Barnhart et al., 2002).

Evidence
level 1a

Surgical treatment
A

Ablation of endometriotic lesions plus

adhesiolysis to improve fertility in minimal
mild endometriosis is effective compared to
diagnostic laparoscopy alone (Jacobson et al.,
2004b).

Evidence
level 1a

The recommendation above is based upon a systematic

review and meta-analysis of two, similar but contradictory
RCTs comparing laparoscopic surgery ( adhesiolysis) with
diagnostic laparoscopy alone. Nevertheless, some members of
the working group questioned the strength of the evidence
because: (i) small numbers were treated in one of the studies
(Parazzini, 1999); (ii) although in the other, larger study
(Marcoux et al., 1997) there was a significantly higher monthly
fecundity rate in the treated compared to the control group,
patients were apparently not blinded to whether they were
treated or not.
2702

IVF

The recommendation above is based on a systematic review

but the working group noted that endometriosis does not
adversely affect pregnancy rates in some large databases (e.g.
SART and HFEA) (Templeton et al., 1996).

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Hormone replacement therapy (HRT) is

recommended after bilateral oophorectomy in
young women but the ideal regimen is
unclear. Adding a progestagen after
hysterectomy is unnecessary but should
protect against the unopposed action of
estrogen on any residual disease. This
theoretical benefit must be balanced against
the small risk of recurrent disease (Matorras
et al., 2002) and the increase in breast cancer
risk reported to be associated with both
tibolone and combined estrogen and
progestagen HRT (Beral and Million Women
Study Collaborators, 2003).

No RCT or meta-analyses are available to

answer the question whether surgical excision
of moderatesevere endometriosis enhances
pregnancy rates. Based upon three studies
(Adamson et al., 1993; Guzick et al., 1997;
Osuga et al., 2002) there seems to be a
negative correlation between the stage of
endometriosis and the spontaneous
cumulative pregnancy rate after surgical
removal of endometriosis, but statistical
significance was only reached in one study
(Osuga et al., 2002).

Evidence
level 1b

Hormone replacement therapy

D

Guideline for diagnosis and treatment of endometriosis

GPP

Laparoscopic ovarian cystectomy is recommended if an ovarian

endometrioma 4 cm in diameter is present to confirm the
diagnosis histologically; reduce the risk of infection; improve
access to follicles and possibly improve ovarian response. The
woman should be counselled regarding the risks of reduced
ovarian function after surgery and the loss of the ovary. The
decision should be reconsidered if she has had previous ovarian
surgery.

Prolonged treatment with a GnRH agonist

before IVF in moderatesevere endometriosis
should be considered and discussed with
patients because improved pregnancy rates have
been reported (Rickes et al., 2002; Surrey et al.,
2002).

Evidence
level 1b

Coping with disease

Complementary therapies
There is evidence from two systematic reviews
suggesting that high frequency transcutaneous
electrical nerve stimulation (TENS),
acupuncture, vitamin B1 and magnesium may
help to relieve dysmenorrhoea (Proctor and
Murphy, 2004; Proctor et al., 2004). Whether
such treatments are effective in endometriosis
associated dysmenorrhoea is unknown.

GPP

Many women with endometriosis report that nutritional

and complementary therapies such as reflexology, traditional
Chinese medicine, herbal treatments, homeopathy etc., do
improve pain symptoms. Whilst there is no evidence from
RCTs in endometriosis to support these treatments, they
should not be ruled out if the woman feels that they
could be beneficial to her overall pain management and/or
quality of life, or work in conjunction with more traditional
therapies.

Evidence
level 4

Patient support groups

GPP

Patient self-help groups can provide invaluable counselling,

support and advice. The website www.endometriosis.org/
support.html provides a comprehensive list of all the self-help
groups in the world.

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